a study of the efficacy and safety of trastuzumab emtansine (trastuzumab-mcc-dm1) vs. trastuzumab (herceptin®) and docetaxel (taxotere®) in patients with metastatic her2-positive breast cancer who have not received prior chemotherapy for metastatic disease

Conditions: Breast Cancer

Summary: this was a phase ii, randomized, multicenter, international, 2-arm, open-label clinical trial designed to explore the efficacy and safety of trastuzumab emtansine (t-dm1) relative to the combination of trastuzumab and docetaxel in patients with human epidermal growth factor receptor 2 (her2)-positive, unresectable, locally advanced breast cancer and/or metastatic breast cancer who have not received prior chemotherapy for metastatic disease.


Eligibility criteria:
inclusion criteria: * histologically or cytologically confirmed adenocarcinoma of the breast with locally advanced or metastatic disease, and a candidate for chemotherapy. * human epidermal growth factor receptor 2 (her2)-positive. * no prior chemotherapy for their metastatic breast cancer (mbc). * measurable disease. * age ≥ 18 years. * for women of childbearing potential and men with partners of childbearing potential, agreement to use a highly effective, non-hormonal form of contraception or 2 effective forms of non-hormonal contraception by the patient and/or partner. contraception use must continue for the duration of study treatment and for at least 6 months after the last dose of study treatment. male patients whose partners are pregnant should use condoms for the duration of the study. exclusion criteria: * history of any chemotherapy for mbc. * an interval of \< 6 months from the completion of cytotoxic chemotherapy in the neo-adjuvant or adjuvant setting until the time of metastatic diagnosis. * trastuzumab ≤ 21 days prior to randomization. * hormone therapy \< 7 days prior to randomization. * current peripheral neuropathy of grade ≥ 3. * history of other malignancy within the last 5 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, stage i uterine cancer, or other cancers with a similar outcome as those previously mentioned. * previous radiotherapy for the treatment of unresectable, locally advanced or metastatic breast cancer is not allowed if more than 25% of marrow-bearing bone has been irradiated or the last fraction of radiotherapy has been administered within approximately 3 weeks prior to randomization. * brain metastases that are untreated, symptomatic, or require therapy to control symptoms or any radiation, surgery, or other therapy to control symptoms from brain metastases within 2 months prior to randomization. * history of exposure to the following cumulative doses of anthracyclines: doxorubicin or liposomal doxorubicin \> 500 mg/m\^2; epirubicin \> 900 mg/m\^2; mitoxantrone \> 120mg/m\^2 and idarubicin \> 90 mg/m\^2. * current unstable angina. * history of symptomatic congestive heart failure, or ventricular arrhythmia requiring treatment. * history of myocardial infarction within 6 months prior to randomization. * left ventricular ejection fraction (lvef) below 50% within approximately 28 days prior to randomization. * history of decreased lvef or symptomatic congestive heart failure (chf) with previous adjuvant trastuzumab treatment. * cardiac troponin i ≥ 0.2 ng/ml within 28 days of randomization. * severe dyspnea at rest because of complications of advanced malignancy or requiring current continuous oxygen therapy. * current severe, uncontrolled systemic disease (eg, clinically significant cardiovascular, pulmonary, or metabolic disease; wound healing disorders; ulcers; or bone fractures). * major surgical procedure or significant traumatic injury within approximately 28 days prior to randomization or anticipation of the need for major surgery during the course of study treatment. * current pregnancy or lactation. * history of receiving any investigational treatment within approximately 28 days prior to randomization. * current known infection with human immunodeficiency virus (hiv), active hepatitis b and/or hepatitis c virus. * history of intolerance (including grade 3-4 infusion reaction) or hypersensitivity to trastuzumab, murine proteins, or docetaxel. * known hypersensitivity to any of the study drugs, including the excipients, or any drugs formulated in polysorbate 80. * assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol.

Keywords: her2-positive breast cancer her2 herceptin taxotere mbc breast cancer tdm1 tdm-1 her2-positive her2+ her2 positive breast cancer her2+ breast cancer armed herceptin trastuzumab emtansine trastuzumab dm1